Europe Faces Persistent Gaps in International GCP Inspections

One of the most striking finds of the report just released by the European Medicines Agency on clinical trials conducted beyond Europe is the number of trial sites – and how few of them are inspected. Across the countries where data was generated for applications for European marketing authorizations trials there were 70,291 sites. Of these, just 357 were inspected between 1997 and 2011. As the agency comments, this is "a very small sample of sites." But no more can be inspected with current resources, it admits. "Further increase in inspections will require not only additional GCP inspection resources from the EU's member states but also to promote international collaboration to improve the inspection coverage and capacity building activities to support and strength local supervision in every country."

Given the concerns repeatedly expressed over compliance with good clinical practice in non-EU countries, the low proportion of checking is all the more striking. Add to that the fact that nearly two-thirds of patients in pivotal trials submitted in marketing authorization applications to the agency over this period were from non-EU countries, and the issue assumes even greater significance for the quality of data generation and trial methodology that underpins many EU authorisations.

The number of inspections is increasing – both as a matter of routine, and in response to specific requests. Top of the list in terms of the proportion of inspections carried out was the USA (21.57%), followed a long way behind – with less than 5% of inspections - by India, Canada, Russia, and then, with less than 2% of inspections, by China, the Philippines, South Africa, Mexico, Thailand, Ukraine, and Brazil. The figures broadly reflect the countries that contributed most to pivotal trials included in authorizations submitted to the agency. Again, the US tops the list – a third of all patients were in North America, compared to less than ten percent in the Middle East/Asia/Pacific region and less than ten percent in Central/South America.

The report is based on more than 1,340 trials from around 677 authorization applications. "The key to the process is therefore to test, by sampling, the processes and systems for different regions/regulatory frameworks, companies, therapeutic areas, population types (pediatric, adult, elderly, in-patient/out-patient), orphan product, commercial or academic sponsor, etc., rather than validating sites per se," says the agency. But it remarks on the "growing concern both among regulators and in public debate about how well these trials are conducted from an ethical and scientific/organisational standpoint, including good clinical practice compliance and about the available framework for the supervision of these trials."